We have obtained all necessary animal protocol permissions and reagents necessary to begin this project. The cell lines being used are the highly immunogenic melanoma and renal cell carcinoma cell lines. In addition, lung cancer cell lines, which are less immunogenic are being used as a comparison. In preliminary experiments, we have determined the number of cells necessary for implant in order to generate tumors for treatment. We have also determined the optimal dose of radiation for control experiments. In ongoing experiments, we are varying the time of administration of anti-PD1 and anti-CTLA4 antibodies relative to radiation to determine if there is any effect on tumor response. In addition, we have obtained an animal protocol to test Toll-like receptor 7 and 8 agonists with radiation in a similar manner to that described above. Toll-like receptors (TLRs) recognize molecular patterns associated with pathogens. After recognition of these patterns, TLRs signal the innate immune system to increase surveillance and attack.